Strict Independence of Parallel and Poly-synaptic Axon-Target Matching during Visual Reflex Circuit Assembly

Abstract

The use of sensory information to drive specific behaviors relies on circuits spanning long distances that wire up through a range of axon-target recognition events. Mechanisms assembling poly-synaptic circuits and the extent to which parallel pathways can "cross-wire" to compensate for loss of one another remain unclear and are crucial to our understanding of brain development and models of regeneration. In the visual system, specific retinal ganglion cells (RGCs) project to designated midbrain targets connected to downstream circuits driving visuomotor reflexes. Here, we deleted RGCs connecting to pupillary light reflex (PLR) midbrain targets and discovered that axon-target matching is tightly regulated. RGC axons of the eye-reflex pathway avoided vacated PLR targets. Moreover, downstream PLR circuitry is maintained; hindbrain and peripheral components retained their proper connectivity and function. These findings point to a model in which poly-synaptic circuit development reflects independent, highly stringent wiring of each parallel pathway and downstream station.

Developmental distribution of primary cilia in the retinofugal visual pathway

“…For example, eye‐specific segregation and spontaneous retinal wave activity occur prenatally in monkeys in contrast to before eye‐opening in mice, indicating a species‐dependent difference in axon mapping and rearrangement in the dLGN during development (Hong & Chen, 2011; Huberman et al, 2008). Furthermore, about 10% of RGCs project to the SC in primates compared to about 90% in mice, a striking contrast (Perry & Cowey, 1984; Seabrook, Burbridge, et al, 2017; Seabrook, Dhande, et al, 2017). Such differences in visual circuitry between species necessitate analysis of primary tissue from primates.…”

“…The two main retinorecipient brain targets in mammals are the superior colliculus (SC) and the dorsal lateral geniculate nucleus (dLGN) (Figure 1a) (Martersteck et al, 2017; Seabrook, Burbridge, Crair, & Huberman, 2017; Seabrook, Dhande, et al, 2017). Because Arl13b and Centrin2 are localized to primary cilia and basal bodies, respectively, they have served as surrogate markers for those ciliary structures (Kasahara et al, 2014; Paoletti, Moudjou, Paintrand, Salisbury, & Bornens, 1996).…”